Macrophages affect immune inflammation and proliferation in benign prostatic hyperplasia via androgen receptor and CD40/CD40L signaling pathway

Copyright © 2020. Published by Elsevier Ltd..

OBJECTIVE: Considering the association of macrophage migration inhibitory factor with development of prostate diseases, this study aims to explore the effect and mechanism of macrophages (MAs) in inflammation and proliferation of benign prostate hyperplasia (BPH) cells.

METHODS: Totally 85 prostate tissues (75 from BPH patients and 10 from brain death patients) were collected for determination of biomarkers of T lymphocyte (CD4 and CD8), B lymphocyte (CD20) and MAs (CD68), as well as androgen receptor (AR) and CD40/CD40L. MAs stimulated by phorbol myristate acetate (PMA) were cultured with BPH cells (BPH-1), followed by AR inhibitor or anti-CD40 L antibody treatment. Proliferation and cell apoptosis were observed by MTT assay, colony formation assay and flow cytometer. Expressions of apoptotic related proteins and MAPK signaling pathway-related proteins were determined by qRT-PCR and Western blot.

RESULTS: BPH tissues had increased expressions of AR, CD40 and CD40 L, as well as elevated expressions of inflammation biomarkers (CD4, CD8, CD20 and CD68) in comparison to normal prostate tissues. MAs could increase the expressions of lymphocytes and inflammation biomarkers, in addition to promoting cell proliferation and inhibiting cell apoptosis. Cell proliferation and inflammation reaction could be attenuated by anti-CD40 L antibody and AR inhibitor in a concentration dependent manner through inhibiting the phosphorylation of JNK, ERK1/2 and p38.

CONCLUSION: MAs regulate AR and CD40/CD40L expression to promote the inflammation and proliferation as well as inhibiting apoptosis of BPH-1 cells through activation of the MAPK signaling pathway. This conclusion may provide a therapeutic strategy for BPH patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:64

Enthalten in:

Tissue & cell - 64(2020) vom: 20. Juni, Seite 101343

Sprache:

Englisch

Beteiligte Personen:

Yang, Minggen [VerfasserIn]
Xu, Zhenqiang [VerfasserIn]
Zhuang, Zhiming [VerfasserIn]

Links:

Volltext

Themen:

147205-72-9
AR protein, human
Androgen receptor pathway
Apoptosis
Benign prostate hyperplasia
CD40/CD40L pathway
CD40 Ligand
EC 2.7.12.2
Inflammation
Journal Article
Macrophages
Mitogen-Activated Protein Kinase Kinases
Proliferation
Receptors, Androgen

Anmerkungen:

Date Completed 15.12.2020

Date Revised 15.12.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.tice.2020.101343

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM310541603